Molecular biology techniques can be employed for an effective detection at molecular level to predict prognosis in patients with malignant tumor, and then, for a proper individual treatment of these diseases. Lung cancer is a common cancer worldwide, the incidence rate in male is 18%, while 21% in female. In 2005, approximate 500,000 new cases of lung cancer occurred in China (about 330,000 cases for male and 170,000 cases for female). The mortality of lung cancer is high, over 900,000 patients die from lung cancer each year (Parkin D M 1999). Therein, 15-20% of lung cancer cases are due to small cell lung cancer. Compared to non small cell lung cancer, small cell lung cancer is of unique morpha, substructure, immunohistochemical features and is classified as a kind of neuroendocrine tumors (Morita T 1990). The disease progresses rapidly, meanwhile, it is sensitive to the first course of radiotherapy and chemotherapy and the response rate is up to 60-80%, but it relapses soon after the treatment, and then becomes resistant to radiotherapy and chemotherapy. Only the patients who have small cell lung cancer at 15-25% limited stage and less than 5% extensive stage survive another five years via the treatment (Sandler A B 2003). In addition, 25-40% of the patients having small cell lung cancer are more than 70 years old at diagnosis. The patients poorly tolerate the chemotherapy because of complications and the like, and are badly prognosticated due to the limited treatment means, so their median survival time is only 10 months (Sekine I 2004). Therefore, there is an urgent need to develop a new treatment strategy which can improve the prognosis of small cell lung cancer.
Molecular targeted therapy has been a hot research point in recent years, and has made a breakthrough in treatment of some malignant tumors. For example, Gefinitib (Iressa) was used in non small cell lung cancer treatment, and the prognosis was good, especially for those patients who are female, do not smoke and suffer from adenocarcinoma; and Imatinib was used in treatment of gastrointestinal stromal tumors, and the better therapeutic effect had been obtained especially for those with Kit exon 11 mutations (Nilsson B 2007); and a combination of C225 and radiotherapy was employed in treatment of locally advanced head and neck cancer, and the survival rate was increased nearly 1 time than that of using radiotherapy alone (Bonner J A 2006). Therefore, it will be a great help for improving patient's prognosis to further understand the molecular mechanism of small cell lung cancer. Fischer et al. (Fischer B 2007) summarized the molecular mechanism studies of small cell lung cancer in recent 20 years: the molecular pathways involved in small cell lung cancer consist of mainly two pathways, PI3K/Akt/mTOR and RAS/MAPK, which are activated through binding of the cell surface receptor tyrosine kinases (RTKs) and their corresponding extracellular growth factors, wherein the RTKs mainly include IGF-IR, EGFR, VEGFR, PDGFR, c-MET. Thus, theoretically, inhibition of the growth of small cell lung cancer can be achieved through inhibition of RTKs or key targets in the pathways. However, it is a pity that no desired clinical effect has been obtained yet. In view of this, it may be a breakthrough for treatment to understand other aspects of the molecular mechanisms in small cell lung cancer.
Small RNA molecule (MicroRNA) generally consists of 18-25 nucleotides, which is a non-coding RNA molecule and can inhibit mRNA function and regulate translation process by binding to said target mRNA. Since 2005, a small amount of literatures on the relationship of microRNA and prognosis have been published, and have confirmed in chronic lymphoma, acute myeloid leukemia, non-small cell lung cancer, pancreatic cancer and neuroblastoma, colon cancer, that prognosis is significantly influenced by microRNA. However, studies on the effects of microRNA on the prognosis of small cell lung cancer have not yet been reported.
MicroRNA-150 (miR-150 for short), containing 22 nucleotides, locates on chromosome 19 and its sequence is shown as SEQ ID NO. 1: 5′-UCUCCCAACCCUUGUACCAGUG-3′, with GenBank accession No. NT—011109.15, (sequence 22272232˜22272315), which is commonly expressed in mature lymphocytes. As reported by Xiao C in 2007, the main function of microRNA-150 is to control the growth and differentiation of B lymphocytes by regulating c-Myb transcription factor. MicroRNA-886-3p (miR-886-3p for short), containing 21 nucleotides, locates on chromosome 5, and its sequence is shown as SEQ ID No. 2: 5′-CGCGGGUGCUUACUGACCCUU-3′, with GenBank accession No. NT—034772.5 (sequence 3783,1310˜3783,1190), the function of which has not been reported in the literature.